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World Journal of Cardiology World J Cardiol 2016 December 26; 8(12): 728-734 ISSN 1949-8462 (online)
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MINIREVIEWS
Newer perspectives of coronary artery disease in young Amitesh Aggarwal, Saurabh Srivastava, M Velmurugan a prevalence of 5% to 10%. Conventional risk factors such as smoking, diabetes, hypertension, obesity and family history seems to be as important as in older CAD subjects. But the prevalence of these risk factors seems to vary in younger subjects. By far the most commonly associated risk factor is smoking in young CAD. Several genes associated with lipoprotein metabolism are now found to be associated with young CAD like cholesterol ester transfer protein (CETP ) gene, hepatic lipase gene, lipoprotein lipase gene, apo A1 gene, apo E gene and apo B . Biomarkers such as lipoprotein (a), fibrinogen, D-dimer, serum Wnt, gamma glutamyl transferase, vitamin D2 and osteocalcin are seems to be associated with premature CAD in some newer studies. In general CAD in young has better prognosis than older subjects. In terms of prognosis two risk factors obesity and current smoking are associated with poorer outcomes. Angiographic studies shows predominance of single vessel disease in young CAD patients. Like CAD in older person primary and secondary prevention plays an important role in prevention of new and further coronary events.
Amitesh Aggarwal, M Velmurugan, Department of Medicine, University College of Medical Sciences and GTB Hospital, Delhi 110095, India Saurabh Srivastava, Department of Medicine, School of Medical Sciences and Research, Sharda University, Noida 201308, India Author contributions: All authors contributed to this paper. Conflict-of-interest statement: None. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/ Manuscript source: Invited manuscript Correspondence to: Amitesh Aggarwal, MD, Associate Professor, Department of Medicine, University College of Medical Sciences and GTB Hospital, Dilshad Garden, Delhi 110095, India. [email protected] Telephone: +91-11-22586262
Key words: Young; Coronary artery disease; Risk factors; Epidemiological trends; Prognosis © The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Received: June 29, 2016 Peer-review started: July 1, 2016 First decision: September 5, 2016 Revised: October 14, 2016 Accepted: November 1, 2016 Article in press: November 2, 2016 Published online: December 26, 2016
Core tip: Coronary artery disease (CAD) in patients less than 45 years of age is termed young CAD. South Asians especially Indians are more vulnerable to have CAD in young age group. Although conventional risk factors, mainly smoking, are also important in young CAD but there are numerous other factors that are responsible for it. Several genes associated with lipopro tein metabolism are now found to be associated with young CAD. Gamma glutamyl transferase, vitamin D2 and osteocalcin seem to be associated with premature CAD in some studies. Angiographic studies shows predominance of single vessel disease in young CAD patients.
Abstract Coronary artery disease (CAD) occurring in less than 45 years of age is termed as young CAD. Recent studies show a prevalence of 1.2% of CAD cases in this age group. Ethnic wise south Asians especially Indians are more vulnerable to have CAD in young age group with
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Aggarwal A et al . Newer perspectives of coronary artery disease in young Aggarwal A, Srivastava S, Velmurugan M. Newer perspectives of coronary artery disease in young. World J Cardiol 2016; 8(12): 728-734 Available from: URL: http://www.wjgnet. com/1949-8462/full/v8/i12/728.htm DOI: http://dx.doi. org/10.4330/wjc.v8.i12.728
Table 1 Spectrum of terminology for young coronary artery disease No.
INTRODUCTION Coronary artery disease (CAD) occurring below the [1] age of 45 years is termed as young CAD . However various studies had considered the age limit varying from 35 years to 55 years in the spectrum of young [2-10] CAD (Table 1). This arena of cardiology has gained importance very recently due to increased prevalence in this age group over a last few decades, with varying risk factor profiles and difference in prognosis as well as longevity after an acute coronary episode. Recently, apart from the established biomarkers of CAD, many new markers, specifically associated with young CAD are discovered. The purpose of this review is to analyse the changing epidemiological trends, role of conventional and newer risk factors and prognosis of young CAD population.
Age group studied
Ref.
1 2 3 4 5
Young CAD Young CAD Young CAD Very young CAD Premature CAD
Ericsson et al[2] Konishi et al[3] Gupta et al[4] Christus et al[5] van Loon et al[6]
6 7 8
Premature CAD Premature CAD Precocious CAD
9
Early onset CAD
Less than 45 yr Less than 40 yr 15-39 yr ≤ 35 yr Men ≤ 45 yr Female ≤ 55 yr Less than 60 yr Less than 45 yr 2 case reports of familial CAD of 29 and 31 yr Less than 45 yr
Genest et al[7] Pineda et al[8] Norum et al[9] Iribarren et al[10]
CAD: Coronary artery disease.
single vessel disease and 3 had double vessel disease) in a study done in Korea. The occult CAD in these individuals was defined by performing coronary CT [18] angiography . The mean age of onset of CAD in Southeast Asians seems to be 53 years as compared to European [19] figure of 63 years . South Asians especially Indians are at greater risk of developing CAD at a young age (5% to 10%) when compared to other ethnic groups [20] (approximately 1% to 2%) . Reported prevalence of young CAD under the age of 40 years, in a study published from Indian subcontinent, in 1991 was 5% to 10%. This vulnerability of Indians to coronary events may be related to life style, environmental and genetic [20] factors . The median age of presentation of CAD in young women is higher when compared to men. Singapore myocardial infarction registry of CAD in group less than 65 years showed that men have 4 times greater risk of [21] CAD than women . In Asians 9.7% males and 4.4% females develop first episode of MI under 40 years of [20] age .
TRENDS IN EPIDIMIOLOGICAL PROFILE Coronary heart disease is the leading cause of morbidity and mortality, worldwide both in developing as well as developed countries, and is responsible for one third or more of all deaths in individuals greater than 35 years [11,12] of age . World Health Organisation has projected that burden due to CAD is going to increase globally from 47 million disability adjusted life years (DALYs) in 1990 to about 82 million DALYs in 2020. Many studies have demonstrated that young CAD contributes to [13] 2% to 6% of all acute coronary events . In the early 1980s, the Framingham study (FHS) reported a 10 year CAD incidence of 12.9 per 1000 in the age of 30 to 34 years and 5.2 per 1000 in the age group 35 to 44 [14] years, in men and women respectively . Studies have shown an increased prevalence of CAD in the subjects with family history of premature [15] CAD, than in general population (35% vs 14%) . The original as well as offspring cohort data of Framingham study, by National heart lung and blood institute (NHLBI’s), from 1880 to 2003 revealed an annual incidence of cardiovascular disease of 3 per 1000 men [16] between 35 to 44 years of age . Centre of disease control prevalence data for the year 2010 revealed that prevalence of CAD in the age group of 18 to 44 years, 45 to 64 years and more than 65 years was 1.2%, [17] 7.1% and 19.8% respectively . Epidemiological data of United Kingdom published in the year 2000, reported a prevalence of 0.5% and 0.18% in men and women [1] between 35 to 44 years respectively . The prevalence of occult CAD in 112 asymptomatic young individuals, less than 40 years of age, was found to be 11% (9 had
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Terminology
RISK FACTORS PROFILE Conventional risk factors (Table 2)
Prevalence of conventional risk factors like diabetes, hypertension, smoking, dyslipidemia and obesity accounts for about 85% to 90% of premature CAD [22] patients . Often young CAD patients have multiple [23] coexisting risk factors contributing to the disease . The most common risk factor associated with young CAD seems to be smoking. The prevalence of smoking in younger individuals less than 45 years of age, with CAD, was reported to be 60% to 90% as compared to 24% [13,24] to 56% in subjects greater than 45 years . Smoking in presence of additional risk factors like diabetes, hypertension and obesity predispose a young individual [25] to increased risk of future acute coronary events . The prevalence of diabetes and hypertension seems to higher in young patients with CAD than without CAD. The prevalence of hypertension is 25% in young
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circumference . Family history of premature CAD is an important risk factor for young CAD. It stresses the role of genes in the aetiology of young CAD. Studies have shown that person with a positive family history of premature CAD tend to have severe coronary atherosclerosis and is a [32] very strong predictor of future acute coronary event . The atherosclerosis in coronary vessels, as revealed by increased plaque content is seen in individuals with a positive family history of premature CAD and increases [32] the incidence of severe obstructive CAD . One study revealed around 64% of young CAD patients had a [13] positive family history . The prevalence of conventional risk factors like hypertension (67%), dyslipidemia (67%), obesity (53%), smoking (42%), and diabetes (33%) is higher [33] in women with a family history of CAD .
Table 2 List of conventional and newer risk factors in young coronary artery disease discussed in the review Conventional risk factors Age Sex Hypertension Diabetes mellitus Dyslipidaemia Obesity Smoking Family history of premature CAD
Newer risk factors Polymorphisms in CETP gene Hepatic lipase gene Lipoprotein lipase gene C-reactive protein gene Apo A1 gene Apo B gene Apo E gene HIF1A gene Factor 5 leiden MTHFR gene Methionine synthase gene Cocaine use Lipoprotein-a, Fibrinogen and D-dimer Decreased serum Wnt Increased gamma glutamyl transferase Raised vitamin D2 and D3 Decreased osteocalcin Hypothyroidism Systemic lupus erythematosis Rheumatoid arthritis HIV patients on HAART Homocysteinemia Kawasaki disease in childhood, Patent foramen ovale Spontaneous coronary artery dissection
Other risk factors
There are numerous risk factors found to be associated with CAD in younger people. Some of the newer risk factors are discussed in the review. Polymorphisms in cholesterol ester transfer protein (CETP) gene, hepatic lipase gene, lipoprotein lipase gene, C-reactive protein gene, apo A1 gene, apo E gene, apo B, hypoxia inducible factor 1 alpha gene, factor 5 leiden, Methylene tetrahydrofolate reductase (MTHFR) gene and methion ine synthase gene have been associated with premature [34-38] CAD . [39] Kuivenhoven et al found a significant association between variation at the CETP locus and angiographic progression of coronary atherosclerosis in men with CHD. The ApoE4 allele has been associated with CAD in several populations. ApoE2/E2 homozygous individuals are at risk for type III hyperlipoproteinemia, which is [40,41] associated with an increased risk for atherosclerosis . Homozygosity for the MTHFR C677T mutation has been associated with elevated levels of homocysteine, and homocysteine levels have been associated with [42,43] CAD risk . Hepatic lipase (HL) is both a phospholipase and a triglyceride lipase and plays an important role in HDL metabolism and in the conversion of VLDL to LDL. Single nucleotide polymorphisms in the HL gene have been shown to associate with plasma lipid concen [44] trations and increased CHD risk . Hypercholesterolemia is the most common and treatable cause of heart disease. Familial Hypercholestero lemia (FH) results from mutations in the LDL receptor, ApoB, PCSK9, and ApoE genes. FH is characterized by isolated elevation of plasma low-density lipoprotein cholesterol and is associated with high risk of premature [45] cardiovascular disease . The prevalence of premature arcus senilis (16.1%), premature greying (34.9%) and premature balding (22.3%) have been found to be significantly increased in young CAD patients when compared to non CAD
CETP: Cholesterol ester transfer protein; HAART: Highly active anti retroviral therapy; MTHFR: Methylene tetrahydrofolate reductase; HIF1A: Hypoxia inducible factor 1 alpha.
CAD as compared to 13% without CAD. Similarly, the incidence of diabetes and pre diabetes is 14.3% and 7.6% in young CAD as compared to only 5.4% and [26] 4.3% in patients without CAD respectively . However, prevalence of these risk factors is much higher in older [27-29] individuals with CAD as compared to young CAD . Various studies have demonstrated a recent increase in the prevalence of hypertension [8.86% (2001-2002) to 27.7% (2009-2010)] and dysglycemia [7.6% [30] (2001-2002) to 36.15% (2009-2010)] in young CAD . Although, dyslipidemia is an important risk factor for young CAD, there seems to be a little difference in prevalence of lipid abnormalities in younger and older patients. One study demonstrated a significantly increased level of LDL and total cholesterol in persons of CAD more than 55 years of age when compared with [27] less than 55 years of age . Conversely in an another study there is high prevalence of lipid abnormalities [28] in young CAD when compared to older CAD group . These differences in lipid parameters may due effect of dietary, genetic and environmental factors on lipid metabolism. Obesity is a well established risk factor for CAD. There is little difference in the prevalence of obesity in [28] young CAD when compared with older CAD patients . Sagittal abdominal diameter to skin fold ratio seems to be a good indicator in predicting premature CAD, even better than body mass index (BMI) and waist
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[58-60]
subjects of same age . Thus young CAD patients are associated with premature ageing as depicted by these markers. The arcus senilis is also a marker of familial hypercholesterolemia which in turn is a risk factor for premature CAD. Cocaine use is also considered as a risk factor for CAD, it is associated with a number of cardiovascular diseases, including myocardial infarction, heart failure, cardiomyopathies, arrhythmias, aortic dissection, and [47] endocarditis . Young CAD patient shows an increased serum levels of lipoprotein-a, fibrinogen and D-dimer as compared [8] to age matched controls . Decreased serum Wnt, increased gamma glutamyl transferase, raised vitamin D2 and D3 and decreased levels of osteocalcin are [48-50] found to be associated with premature CAD . This association of CAD in young with high levels of vitamin D is in contradiction to the studies done in general population where deficiency of vitamin D is associated [51-53] with adverse cardiovascular outcomes . Diseases such as hypothyroidism, systemic lupus erythematosis, rheumatoid arthritis, HIV patients on highly active anti retroviral therapy (HAART) (especially with protease inhibitors), homocysteinaemia, kawasaki disease in childhood, patent foramen ovale (causing paradoxical embolism) and various other conditions are [54,55] found to associated with accelerated atherosclerosis . The mean age of presentation of spontaneous coronary artery dissection is 35-40 years, and is more common in females. The patients are divided into three groups: A peripartum, atherosclerotic and idiopathic [56] group . Dissection occurs in tunica intima of coronary arteries, the blood penetrates and results in intramural hematoma in tunica media, resulting in restriction in the size of lumen, reduction of blood flow and myocardial [57] infarction .
CAD
PROGNOSIS Obesity and current smoking are the two important conventional risk factors associated with adverse outcomes in the form of increased mortality and future [3] acute coronary events . Mortality of CAD in people of China, less than 40 years of age, was 13.81/100000 [61] in 2006 which increased to 19.07/100000 in 2009 . There is a widespread decrease in mortality due to CAD in older age group in the recent years but it not seen in [62] CAD in younger age group . The possible explanation that is proposed is increase in prevalence of risk factors such as diabetes, obesity and hypertension in younger [62] age groups . Mortality after an acute coronary event is two times higher in women than in men under 50 years [63,64] of age . The cause of increased incidence of adverse event in women with premature CAD is still unknown. In patient with acute coronary event both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are associated with excellent immediate survival (mortality of 0.8% vs 1.4% for PCI and CABG respectively at 30 d) as well as [65] long term survival outcomes at end of 5 years . But PCI seems to associated with lower rate of repeated acute coronary events and revascularisation procedures when compared to CABG at the end of 5 years (repeat myocardial infarction 89.9% vs 96.6% for PCI vs [66] CABG) . Mortality outcomes at 30 d and 3 years after an ST segment elevation myocardial infarction in 3601 patients with and without family history of premature CAD were compared in Harmonizing outcomes with revascularization and stents in acute myocardial infarction (HORIZONS-AMI) trial, which did not show any significant association of family history of premature [67] CAD with mortality outcomes . In patients with young CAD high C-reactive protein have been associated recurrence of future acute coronary event and raised fibrinogen levels seems to be associated with increased [6] mortality . Persons with positive family history of premature CAD and coronary artery calcium scores th greater than 80 percentiles benefit from treatment with statins for primary prevention of acute coronary [68] events . Young CAD patients have higher rates of normal coronary vessels on angiography, mild luminal irregu larities and increased prevalence of single vessel disease [24] than older CAD patients . In recent study from Nepal of young CAD less than 45 years angiography revealed 7.6% had normal or non critical disease, 6.1% had triple vessel disease, 36.9% had double vessel disease [69] and 53.8% had single vessel disease . Single vessel disease involving left anterior des cending artery is much more common in young women [70,71] when compared with young men with CAD . The prevalence of normal coronary arteries in patients with young CAD is about 8% to 22% as reported in [72-74] various studies compared to 3% to 4% in general
PATHOPHYSIOLOGY OF CAD IN YOUNG Conventional CAD accounts for about 80% of CAD in young adults. About 4% of heart attacks in young adults are due to congenital abnormalities of the coronary artery anatomy, about 5% due to blood clots that originate elsewhere and are carried to otherwise normal coronary arteries, and block the artery, in another 5%, various disorders of the blood clotting system increase the risk of clot formation. The remaining 6% of CAD in young adults is due to spasm or inflammation of the coronary arteries, radiation therapy for chest tumors, chest trauma, and abuse of cocaine, amphetamines, and other drugs. Coronary segments, with non-signifi cant stenosis and non calcified plaque, shows positive remodeling that might be the cause of CAD in young individuals with normal coronary artery. Positive remodeling is related to plaque instability, suggesting it is more prone to rupture and erosion with subsequent coronary events. Lipid core plaques, in contrast to the severely calcified plaques, showed positive vascular remodeling, thus early plaques are more prone for
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CAD population . The cause of this high prevalence of normal angiography in young CAD patients is still unclear. The probable reason could be the natural extra luminal progression of disease in the initial stages, as the vessel wall compensates to maintain unrestricted luminal [76] blood flow . An occlusive thrombus produced by the rupture of an angiographically “invisible” vulnerable plaque totally lysed after few hours or a long-lasting vasospasm leading to complete occlusion of a normal coronary artery or a combination of these two are the most likely mechanism of CAD in patient with normal [77] coronaries .
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CONCLUSION The overall prevalence of CAD including the subset of young CAD is on decreasing trend but mortality of CAD doesn’t seems to be decreasing when comparing to older CAD patients. In addition to conventional risk factors numerous other risk factors and genes play an important role in the causation of the disease. The prognosis of CAD in younger people is better than older people. Current smoking and obesity have major impact in long term mortality and morbidity. Young CAD patients with an acute coronary event undergoing PCI and CABG have an excellent immediate and long term survival rates.
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REFERENCES 1 2
3
4
5
6
7
8
Egred M, Viswanathan G, Davis GK. Myocardial infarction in young adults. Postgrad Med J 2005; 81: 741-745 [PMID: 16344295 DOI: 10.1136/pgmj.2004.027532] Ericsson CG, Hamsten A, Nilsson J, Grip L, Svane B, de Faire U. Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet 1996; 347: 849-853 [PMID: 8622389 DOI: 10.1016/ S0140-6736(96)91343-4] Konishi H, Miyauchi K, Kasai T, Tsuboi S, Ogita M, Naito R, Katoh Y, Okai I, Tamura H, Okazaki S, Daida H. Long-term prognosis and clinical characteristics of young adults (≤40 years old) who underwent percutaneous coronary intervention. J Cardiol 2014; 64: 171-174 [PMID: 24495504 DOI: 10.1016/j.jjcc.2013.12.005] Gupta R, Misra A, Vikram NK, Kondal D, Gupta SS, Agrawal A, Pandey RM. Younger age of escalation of cardiovascular risk factors in Asian Indian subjects. BMC Cardiovasc Disord 2009; 9: 28 [PMID: 19575817 DOI: 10.1186/1471-2261-9-28] Christus T, Shukkur AM, Rashdan I, Koshy T, Alanbaei M, Zubaid M, Hayat N, Alsayegh A. Coronary Artery Disease in Patients Aged 35 or less - A Different Beast? Heart Views 2011; 12: 7-11 [PMID: 21731802 DOI: 10.4103/1995-705X.81550] van Loon JE, de Maat MP, Deckers JW, van Domburg RT, Leebeek FW. Prognostic markers in young patients with premature coronary heart disease. Atherosclerosis 2012; 224: 213-217 [PMID: 22818563 DOI: 10.1016/j.atherosclerosis.2012.06.067] Genest JJ, McNamara JR, Salem DN, Schaefer EJ. Prevalence of risk factors in men with premature coronary artery disease. Am J Cardiol 1991; 67: 1185-1189 [PMID: 2035438 DOI: 10.1016/00029149(91)90924-A] Pineda J, Marín F, Marco P, Roldán V, Valencia J, Ruiz-Nodar JM, Sogorb F, Lip GY. Premature coronary artery disease in young (age & lt; 45) subjects: interactions of lipid profile, thrombophilic and haemostatic markers. Int J Cardiol 2009; 136: 222-225 [PMID: 18625524 DOI: 10.1016/j.ijcard.2008.04.020]
WJC|www.wjgnet.com
16
17 18
19
20 21
22
732
Norum RA, Lakier JB, Goldstein S, Angel A, Goldberg RB, Block WD, Noffze DK, Dolphin PJ, Edelglass J, Bogorad DD, Alaupovic P. Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease. N Engl J Med 1982; 306: 1513-1519 [PMID: 7078608 DOI: 10.1056/NEJM198206243062503] Iribarren C, Go AS, Husson G, Sidney S, Fair JM, Quertermous T, Hlatky MA, Fortmann SP. Metabolic syndrome and earlyonset coronary artery disease: is the whole greater than its parts? J Am Coll Cardiol 2006; 48: 1800-1807 [PMID: 17084253 DOI: 10.1016/j.jacc.2006.03.070] Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 2010; 121: 948-954 [PMID: 20177011 DOI: 10.1161/ CIRCULATIONAHA.109.192666] Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: epidemiological update. Eur Heart J 2014; 35: 2929 [PMID: 25381246 DOI: 10.1093/eurheartj/ehu299] Cole JH, Miller JI, Sperling LS, Weintraub WS. Long-term followup of coronary artery disease presenting in young adults. J Am Coll Cardiol 2003; 41: 521-528 [PMID: 12598059 DOI: 10.1016/ S0735-1097(02)02862-0] Kannel WB, Abbott RD. Incidence and prognosis of unrecognized myocardial infarction. An update on the Framingham study. N Engl J Med 1984; 311: 1144-1147 [PMID: 6482932 DOI: 10.1056/ NEJM198411013111802] Kang MK, Chang HJ, Kim YJ, Park AR, Park S, Jang Y, Chung N. Prevalence and determinants of coronary artery disease in first-degree relatives of premature coronary artery disease. Coron Artery Dis 2012; 23: 167-173 [PMID: 22421547 DOI: 10.1097/ MCA.0b013e3283515538] Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Roger VL, Thom T, WasserthielSmoller S, Wong ND, Wylie-Rosett J. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 2010; 121: e46-e215 [PMID: 20019324 DOI: 10.1161/CIRCULATIONAHA.109.192667] Centers for Disease Control and Prevention (CDC). Prevalence of coronary heart disease--United States, 2006-2010. MMWR Morb Mortal Wkly Rep 2011; 60: 1377-1381 [PMID: 21993341] Ha EJ, Kim Y, Cheung JY, Shim SS. Coronary artery disease in asymptomatic young adults: its prevalence according to coronary artery disease risk stratification and the CT characteristics. Korean J Radiol 2010; 11: 425-432 [PMID: 20592926 DOI: 10.3348/ kjr.2010.11.4.425] Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937-952 [PMID: 15364185 DOI: 10.1016/ S0140-6736(04)17018-9] Sharma M, Ganguly NK. Premature coronary artery disease in Indians and its associated risk factors. Vasc Health Risk Manag 2005; 1: 217-225 [PMID: 17319107] Kam R, Cutter J, Chew SK, Tan A, Emmanuel S, Mak KH, Chan CN, Koh TH, Lim YL. Gender differences in outcome after an acute myocardial infarction in Singapore. Singapore Med J 2002; 43: 243-248 [PMID: 12188076] Khot UN, Khot MB, Bajzer CT, Sapp SK, Ohman EM, Brener SJ, Ellis SG, Lincoff AM, Topol EJ. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 2003; 290:
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898-904 [PMID: 12928466 DOI: 10.1001/jama.290.7.898] Celik T, Iyisoy A. Premature coronary artery disease in young patients: an uncommon but growing entity. Int J Cardiol 2010; 144: 131-132 [PMID: 19174320 DOI: 10.1016/j.ijcard.2008.12.150] Zimmerman FH, Cameron A, Fisher LD, Ng G. Myocardial infarction in young adults: angiographic characterization, risk factors and prognosis (Coronary Artery Surgery Study Registry). J Am Coll Cardiol 1995; 26: 654-661 [PMID: 7642855 DOI: 10.1016 /0735-1097(95)00254-2] Aggarwal A, Aggarwal S, Sarkar PG, Sharma V. Predisposing factors to premature coronary artery disease in young (age ≤ 45 years) smokers: a single center retrospective case control study from India. J Cardiovasc Thorac Res 2014; 6: 15-19 [PMID: 24753826] Aggarwal A, Aggarwal S, Goel A, Sharma V, Dwivedi S. A retrospective case-control study of modifiable risk factors and cutaneous markers in Indian patients with young coronary artery disease. JRSM Cardiovasc Dis 2012; 1: pii: cvd.2012.012010 [PMID: 24175065 DOI: 10.1258/cvd.2012.012010] Hatmi ZN, Mahdavi-Mazdeh M, Hashemi-Nazari SS, Hajighasemi E, Nozari B, Mahdavi A. Pattern of coronary artery disease risk factors in population younger than 55 years and above 55 years: a population study of 31999 healthy individuals. Acta Med Iran 2011; 49: 368-374 [PMID: 21874640] Sinha N, Kumar S, Rai H, Singh N, Kapoor A, Tewari S, Saran RK, Narain VS, Bharadwaj RP, Bansal RK, Saxena PC, Sinha PR, Gupta PR, Mishra M, Jain P, Pandey CM, Singh U, Agarwal SS. Patterns and determinants of dyslipidaemia in ‘Young’ versus ‘Not so Young’ patients of coronary artery disease: a multicentric, randomised observational study in northern India. Indian Heart J 2012; 64: 229-235 [PMID: 22664802 DOI: 10.1016/S0019-4832(12)60078-9] Reibis R, Treszl A, Wegscheider K, Bestehorn K, Karmann B, Völler H. Disparity in risk factor pattern in premature versus lateonset coronary artery disease: a survey of 15,381 patients. Vasc Health Risk Manag 2012; 8: 473-481 [PMID: 22930639 DOI: 10.2147/VHRM.S33305] Aggarwal A, Aggarwal S, Sharma V. Cardiovascular Risk Factors in Young Patients of Coronary Artery Disease: Differences over a Decade. J Cardiovasc Thorac Res 2014; 6: 169-173 [PMID: 25320664 DOI: 10.15171/jcvtr.2014.006] Vasheghani-Farahani A, Majidzadeh-A K, Masoudkabir F, Karbalai S, Koleini M, Aiatollahzade-Esfahani F, Pashang M, Hakki E. Sagittal abdominal diameter to triceps skinfold thickness ratio: a novel anthropometric index to predict premature coronary atherosclerosis. Atherosclerosis 2013; 227: 329-333 [PMID: 23466099 DOI: 10.1016/j.atherosclerosis.2013.01.033] Otaki Y, Gransar H, Berman DS, Cheng VY, Dey D, Lin FY, Achenbach S, Al-Mallah M, Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Chinnaiyan K, Chow BJ, Delago A, Hadamitzky M, Hausleiter J, Kaufmann P, Maffei E, Raff G, Shaw LJ, Villines TC, Dunning A, Min JK. Impact of family history of coronary artery disease in young individuals (from the CONFIRM registry). Am J Cardiol 2013; 111: 1081-1086 [PMID: 23411105 DOI: 10.1016/ j.amjcard.2012.12.042] Choi J, Daskalopoulou SS, Thanassoulis G, Karp I, Pelletier R, Behlouli H, Pilote L. Sex- and gender-related risk factor burden in patients with premature acute coronary syndrome. Can J Cardiol 2014; 30: 109-117 [PMID: 24238757 DOI: 10.1016/ j.cjca.2013.07.674] Anderson JL, Horne BD, Camp NJ, Muhlestein JB, Hopkins PN, Cannon-Albright LA, Mower CP, Park JJ, Clarke JL, Nicholas ZP, McKinney JT, Carlquist JF. Joint effects of common genetic variants from multiple genes and pathways on the risk of premature coronary artery disease. Am Heart J 2010; 160: 250-256.e3 [PMID: 20691829] Abd El-Aziz TA, Mohamed RH. Human C-reactive protein gene polymorphism and metabolic syndrome are associated with premature coronary artery disease. Gene 2013; 532: 216-221 [PMID: 24055729 DOI: 10.1016/j.gene.2013.09.042] Kay A, März W, Hoffmann MM, Zhang Q, Masana Ll, Cavanna J, Baroni MG, Shine B, Galton DJ. Coronary artery disease and
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38
39
40
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43
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dyslipidemia within Europe: genetic variants in lipid transport gene loci in German subjects with premature coronary artery disease. Atheroscler Suppl 2002; 3: 27-33 [PMID: 12044583 DOI: 10.1016/ S1567-5688(01)00003-4] López-Reyes A, Rodríguez-Pérez JM, Fernández-Torres J, Martínez-Rodríguez N, Pérez-Hernández N, Fuentes-Gómez AJ, Aguilar-González CA, Alvarez-León E, Posadas-Romero C, Villarreal-Molina T, Pineda C, Vargas-Alarcón G. The HIF1A rs2057482 polymorphism is associated with risk of developing premature coronary artery disease and with some metabolic and cardiovascular risk factors. The Genetics of Atherosclerotic Disease (GEA) Mexican Study. Exp Mol Pathol 2014; 96: 405-410 [PMID: 24769354 DOI: 10.1016/j.yexmp.2014.04.010] Kanth VV, Golla JP, Sastry BK, Naik S, Kabra N, Sujatha M. Genetic interactions between MTHFR (C677T), methionine synthase (A2756G, C2758G) variants with vitamin B12 and folic acid determine susceptibility to premature coronary artery disease in Indian population. J Cardiovasc Dis Res 2011; 2: 156-163 [PMID: 22022143 DOI: 10.4103/0975-3583.85262] Kuivenhoven JA, Jukema JW, Zwinderman AH, de Knijff P, McPherson R, Bruschke AV, Lie KI, Kastelein JJ. The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group. N Engl J Med 1998; 338: 86-93 [PMID: 9420339 DOI: 10.1056/NEJM199801083380203] Nieminen MS, Mattila KJ, Aalto-Setälä K, Kuusi T, Kontula K, Kauppinen-Mäkelin R, Ehnholm C, Jauhiainen M, Valle M, Taskinen MR. Lipoproteins and their genetic variation in subjects with and without angiographically verified coronary artery disease. Arterioscler Thromb 1992; 12: 58-69 [PMID: 1346250 DOI: 10.1161/01. ATV.12.1.58] Eto M, Watanabe K, Makino I. Increased frequencies of apoli poprotein epsilon 2 and epsilon 4 alleles in patients with ischemic heart disease. Clin Genet 1989; 36: 183-188 [PMID: 2791332] Brattström L, Wilcken DE, Ohrvik J, Brudin L. Common methy lenetetrahydrofolate reductase gene mutation leads to hyperhomo cysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 1998; 98: 2520-2526 [PMID: 9843457 DOI: 10.1161/01. CIR.98.23.2520] Danesh J, Lewington S. Plasma homocysteine and coronary heart disease: systematic review of published epidemiological studies. J Cardiovasc Risk 1998; 5: 229-232 [PMID: 9919470 DOI: 10.1097/ 00043798-199808000-00004] Chatterjee C, Sparks DL. Hepatic lipase, high density lipoproteins, and hypertriglyceridemia. Am J Pathol 2011; 178: 1429-1433 [PMID: 21406176 DOI: 10.1016/j.ajpath.2010.12.050] Setia N, Verma IC, Khan B, Arora A. Premature coronary artery disease and familial hypercholesterolemia: need for early diagnosis and cascade screening in the Indian population. Cardiol Res Pract 2012; 2012: 658526 [PMID: 22111029 DOI: 10.1155/2012/658526] Erdoğan T, Kocaman SA, Çetin M, Durakoğlugil ME, Uğurlu Y, Şahin İ, Çanga A. Premature hair whitening is an independent predictor of carotid intima-media thickness in young and middleaged men. Intern Med 2013; 52: 29-36 [PMID: 23291671 DOI: 10.2169/internalmedicine.52.7842] Rezkalla SH, Kloner RA. Cocaine-induced acute myocardial infarction. Clin Med Res 2007; 5: 172-176 [PMID: 18056026 DOI: 10.3121/cmr.2007.759] Shabbir S, Khan DA, Khan FA, Elahi MM, Matata BM. Serum gamma glutamyl transferase: a novel biomarker for screening of premature coronary artery disease. Cardiovasc Revasc Med 2011; 12: 367-374 [PMID: 21454140 DOI: 10.1016/j.carrev.2011.02.001] Goliasch G, Blessberger H, Azar D, Heinze G, Wojta J, Bieglmayer C, Wagner O, Schillinger M, Huber K, Maurer G, Haas M, Wiesbauer F. Markers of bone metabolism in premature myocardial infarction (≤ 40 years of age). Bone 2011; 48: 622-626 [PMID: 21078422 DOI: 10.1016/j.bone.2010.11.005] Goliasch G, Wiesbauer F, Kastl SP, Katsaros KM, Blessberger H, Maurer G, Schillinger M, Huber K, Wojta J, Speidl WS. Premature myocardial infarction is associated with low serum levels of Wnt-1.
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Atherosclerosis 2012; 222: 251-256 [PMID: 22391424 DOI: 10.1016/j.atherosclerosis.2012.02.017] Sood A, Arora R. Vitamin D deficiency and its correlations with increased cardiovascular incidences. Am J Ther 2010; 17: e105-e109 [PMID: 19451805] Michos ED, Melamed ML. Vitamin D and cardiovascular disease risk. Curr Opin Clin Nutr Metab Care 2008; 11: 7-12 [PMID: 18090651 DOI: 10.1097/MCO.0b013e3282f2f4dd] Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Inde pendent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 2008; 168: 1340-1349 [PMID: 18574092 DOI: 10.1001/archinte.168.12.1340] Othman KMS, Assaf NY. Early detection of premature subclinical coronary atherosclerosis in systemic lupus erythematosus patients. The Egyptian Heart Journal 2013; 65: 281-288 [DOI: 10.1016/ j.ehj.2012.12.003] de Saint Martin L, Vandhuick O, Guillo P, Bellein V, Bressollette L, Roudaut N, Amaral A, Pasquier E. Premature atherosclerosis in HIV positive patients and cumulated time of exposure to antiretroviral therapy (SHIVA study). Atherosclerosis 2006; 185: 361-367 [PMID: 16137695 DOI: 10.1016/j.atherosclerosis.2005.06.049] DeMaio SJ, Kinsella SH, Silverman ME. Clinical course and longterm prognosis of spontaneous coronary artery dissection. Am J Cardiol 1989; 64: 471-474 [PMID: 2773790 DOI: 10.1016/0002-91 49(89)90423-2] Dhawan R, Singh G, Fesniak H. Spontaneous coronary artery dissection: the clinical spectrum. Angiology 1979; 53: 89-93 [PMID: 11863314 DOI: 10.1177/000331970205300112] Klein LW. Acute coronary syndromes in young patients with angiographically normal coronary arteries. Am Heart J 2006; 152: 607-610 [PMID: 16996822 DOI: 10.1016/j.ahj.2006.03.020] Tanaka M, Tomiyasu K, Fukui M, Akabame S, KobayashiTakenaka Y, Nakano K, Kadono M, Hasegawa G, Oda Y, Nakamura N. Evaluation of characteristics and degree of remodeling in coronary atherosclerotic lesions by 64-detector multislice computed tomography (MSCT). Atherosclerosis 2009; 203: 436-441 [PMID: 18775536 DOI: 10.1016/j.atherosclerosis.2008.07.013] Kullo IJ, Edwards WD, Schwartz RS. Vulnerable plaque: pathobiology and clinical implications. Ann Intern Med 1998; 129: 1050-1060 [PMID: 9867761 DOI: 10.7326/0003-4819-129-12-199 812150-00010] Yang WX, Yang Z, Wu YJ, Qiao SB, Yang YJ, Chen JL. Factors associated with coronary artery disease in young population (age ≤ 40): analysis with 217 cases. Chin Med Sci J 2014; 29: 38-42 [PMID: 24698677 DOI: 10.1016/S1001-9294(14)60022-5] Nichols M, Townsend N, Scarborough P, Rayner M. Trends in agespecific coronary heart disease mortality in the European Union over three decades: 1980-2009. Eur Heart J 2013; 34: 3017-3027 [PMID: 23801825] Sharma K, Gulati M. Coronary artery disease in women: a 2013 update. Glob Heart 2013; 8: 105-112 [PMID: 25690374 DOI: 10.1016/j.gheart.2013.02.001] Vaccarino V, Badimon L, Corti R, de Wit C, Dorobantu M, Manfrini O, Koller A, Pries A, Cenko E, Bugiardini R. Presentation, management, and outcomes of ischaemic heart disease in women. Nat Rev Cardiol 2013; 10: 508-518 [PMID: 23817188 DOI: 10.1038/nrcardio.2013.93] Fournier JA, Sánchez A, Quero J, Fernández-Cortacero JA, González-Barrero A. Myocardial infarction in men aged 40 years or less: a prospective clinical-angiographic study. Clin Cardiol 1996;
66
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68
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70
71
72
73
74 75
76 77
19: 631-636 [PMID: 8864336 DOI: 10.1002/clc.4960190809] Biancari F, Gudbjartsson T, Heikkinen J, Anttila V, Mäkikallio T, Jeppsson A, Thimour-Bergström L, Mignosa C, Rubino AS, Kuttila K, Gunn J, Wistbacka JO, Teittinen K, Korpilahti K, Onorati F, Faggian G, Vinco G, Vassanelli C, Ribichini F, Juvonen T, Axelsson TA, Sigurdsson AF, Karjalainen PP, Mennander A, Kajander O, Eskola M, Ilveskoski E, D’Oria V, De Feo M, Kiviniemi T, Airaksinen KE. Comparison of 30-day and 5-year outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in patients aged≤50 years (the Coronary aRtery diseAse in younG adultS Study). Am J Cardiol 2014; 114: 198-205 [PMID: 24878127 DOI: 10.1016/j.amjcard.2014.04.025] Ertelt K, Généreux P, Mintz GS, Brener SJ, Kirtane AJ, McAndrew TC, Francese DP, Ben-Yehuda O, Mehran R, Stone GW. Clinical profile and impact of family history of premature coronary artery disease on clinical outcomes of patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: analysis from the HORIZONS-AMI Trial. Cardiovasc Revasc Med 2014; 15: 375-380 [PMID: 25288517 DOI: 10.1016/ j.carrev.2014.09.002] Mulders TA, Sivapalaratnam S, Stroes ES, Kastelein JJ, Guerci AD, Pinto-Sietsma SJ. Asymptomatic individuals with a positive family history for premature coronary artery disease and elevated coronary calcium scores benefit from statin treatment: a post hoc analysis from the St. Francis Heart Study. JACC Cardiovasc Imaging 2012; 5: 252-260 [PMID: 22421169 DOI: 10.1016/ j.jcmg.2011.11.014] Tamrakar R, Bhatt YD, Kansakar S, Bhattarai M, Shaha KB, Tuladhar E. Acute Myocardial Infarction in Young Adults: Study of Risk factors, Angiographic Features and Clinical Outcome. Nepalese Heart Journal 2014; 10: 12-16 [DOI: 10.3126/njh. v10i1.9740] Li Z, Li ZZ, Gao YL, Tao Y, Wang S, Wang Q, Ma CS, DU X. Clinical and coronary angiographic features of young women with acute myocardial infarction. Zhonghua Xinxue Guanbing Zazhi 2012; 40: 225-230 [PMID: 22801268] Liu W, Mukku VK, Liu YY, Shi DM, Zhao YX, Zhou YJ. Longterm follow up of percutaneous coronary intervention of coronary artery disease in women ≤45 years of age. Am J Cardiol 2013; 112: 918-922 [PMID: 23791012 DOI: 10.1016/j.amjcard.2013.05.027] Kaul U, Dogra B, Manchanda SC, Wasir HS, Rajani M, Bhatia ML. Myocardial infarction in young Indian patients: risk factors and coronary arteriographic profile. Am Heart J 1986; 112: 71-75 [PMID: 3728290 DOI: 10.1016/0002-8703(86)90680-0] Gohlke H, Gohlke-Bärwolf C, Stürzenhofecker P, Görnandt L, Thilo A, Haakshorst W, Roskamm H. Myocardial Infarction at young age - correlation of angio-graphic findings with risk factors and history in 619 patients. Circulation 1980; (Suppl III) 62: 39 (abstr) Lim YT, Ling LH, Tambyah PA, Choo MH. Myocardial infarction in patients aged 40 years and below: an angiographic review. Singapore Med J 1996; 37: 352-355 [PMID: 8993130] Agewall S, Eurenius L, Hofman-Bang C, Malmqvist K, Frick M, Jernberg T, Tornvall P. Myocardial infarction with angiographically normal coronary arteries. Atherosclerosis 2011; 219: 10-14 [PMID: 21601856 DOI: 10.1016/j.atherosclerosis.2011.04.036] Chandrasekaran B, Kurbaan AS. Myocardial infarction with angiographically normal coronary arteries. J R Soc Med 2002; 95: 398-400 [PMID: 12151489 DOI: 10.1258/jrsm.95.8.398] Alpert JS. Myocardial infarction with angiographically normal coronary arteries. Arch Intern Med 1994; 154: 265-269 [PMID: 8297192 DOI: 10.1001/archinte.154.3.265] P- Reviewer: Pocar M, Sabate M, Tsai WC S- Editor: Ji FF L- Editor: A E- Editor: Wu HL
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World Journal of Cardiology World J Cardiol 2016 December 26; 8(12): 728-734 ISSN 1949-8462 (online)
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MINIREVIEWS
Newer perspectives of coronary artery disease in young Amitesh Aggarwal, Saurabh Srivastava, M Velmurugan a prevalence of 5% to 10%. Conventional risk factors such as smoking, diabetes, hypertension, obesity and family history seems to be as important as in older CAD subjects. But the prevalence of these risk factors seems to vary in younger subjects. By far the most commonly associated risk factor is smoking in young CAD. Several genes associated with lipoprotein metabolism are now found to be associated with young CAD like cholesterol ester transfer protein (CETP ) gene, hepatic lipase gene, lipoprotein lipase gene, apo A1 gene, apo E gene and apo B . Biomarkers such as lipoprotein (a), fibrinogen, D-dimer, serum Wnt, gamma glutamyl transferase, vitamin D2 and osteocalcin are seems to be associated with premature CAD in some newer studies. In general CAD in young has better prognosis than older subjects. In terms of prognosis two risk factors obesity and current smoking are associated with poorer outcomes. Angiographic studies shows predominance of single vessel disease in young CAD patients. Like CAD in older person primary and secondary prevention plays an important role in prevention of new and further coronary events.
Amitesh Aggarwal, M Velmurugan, Department of Medicine, University College of Medical Sciences and GTB Hospital, Delhi 110095, India Saurabh Srivastava, Department of Medicine, School of Medical Sciences and Research, Sharda University, Noida 201308, India Author contributions: All authors contributed to this paper. Conflict-of-interest statement: None. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/ Manuscript source: Invited manuscript Correspondence to: Amitesh Aggarwal, MD, Associate Professor, Department of Medicine, University College of Medical Sciences and GTB Hospital, Dilshad Garden, Delhi 110095, India. [email protected] Telephone: +91-11-22586262
Key words: Young; Coronary artery disease; Risk factors; Epidemiological trends; Prognosis © The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Received: June 29, 2016 Peer-review started: July 1, 2016 First decision: September 5, 2016 Revised: October 14, 2016 Accepted: November 1, 2016 Article in press: November 2, 2016 Published online: December 26, 2016
Core tip: Coronary artery disease (CAD) in patients less than 45 years of age is termed young CAD. South Asians especially Indians are more vulnerable to have CAD in young age group. Although conventional risk factors, mainly smoking, are also important in young CAD but there are numerous other factors that are responsible for it. Several genes associated with lipopro tein metabolism are now found to be associated with young CAD. Gamma glutamyl transferase, vitamin D2 and osteocalcin seem to be associated with premature CAD in some studies. Angiographic studies shows predominance of single vessel disease in young CAD patients.
Abstract Coronary artery disease (CAD) occurring in less than 45 years of age is termed as young CAD. Recent studies show a prevalence of 1.2% of CAD cases in this age group. Ethnic wise south Asians especially Indians are more vulnerable to have CAD in young age group with
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Aggarwal A et al . Newer perspectives of coronary artery disease in young Aggarwal A, Srivastava S, Velmurugan M. Newer perspectives of coronary artery disease in young. World J Cardiol 2016; 8(12): 728-734 Available from: URL: http://www.wjgnet. com/1949-8462/full/v8/i12/728.htm DOI: http://dx.doi. org/10.4330/wjc.v8.i12.728
Table 1 Spectrum of terminology for young coronary artery disease No.
INTRODUCTION Coronary artery disease (CAD) occurring below the [1] age of 45 years is termed as young CAD . However various studies had considered the age limit varying from 35 years to 55 years in the spectrum of young [2-10] CAD (Table 1). This arena of cardiology has gained importance very recently due to increased prevalence in this age group over a last few decades, with varying risk factor profiles and difference in prognosis as well as longevity after an acute coronary episode. Recently, apart from the established biomarkers of CAD, many new markers, specifically associated with young CAD are discovered. The purpose of this review is to analyse the changing epidemiological trends, role of conventional and newer risk factors and prognosis of young CAD population.
Age group studied
Ref.
1 2 3 4 5
Young CAD Young CAD Young CAD Very young CAD Premature CAD
Ericsson et al[2] Konishi et al[3] Gupta et al[4] Christus et al[5] van Loon et al[6]
6 7 8
Premature CAD Premature CAD Precocious CAD
9
Early onset CAD
Less than 45 yr Less than 40 yr 15-39 yr ≤ 35 yr Men ≤ 45 yr Female ≤ 55 yr Less than 60 yr Less than 45 yr 2 case reports of familial CAD of 29 and 31 yr Less than 45 yr
Genest et al[7] Pineda et al[8] Norum et al[9] Iribarren et al[10]
CAD: Coronary artery disease.
single vessel disease and 3 had double vessel disease) in a study done in Korea. The occult CAD in these individuals was defined by performing coronary CT [18] angiography . The mean age of onset of CAD in Southeast Asians seems to be 53 years as compared to European [19] figure of 63 years . South Asians especially Indians are at greater risk of developing CAD at a young age (5% to 10%) when compared to other ethnic groups [20] (approximately 1% to 2%) . Reported prevalence of young CAD under the age of 40 years, in a study published from Indian subcontinent, in 1991 was 5% to 10%. This vulnerability of Indians to coronary events may be related to life style, environmental and genetic [20] factors . The median age of presentation of CAD in young women is higher when compared to men. Singapore myocardial infarction registry of CAD in group less than 65 years showed that men have 4 times greater risk of [21] CAD than women . In Asians 9.7% males and 4.4% females develop first episode of MI under 40 years of [20] age .
TRENDS IN EPIDIMIOLOGICAL PROFILE Coronary heart disease is the leading cause of morbidity and mortality, worldwide both in developing as well as developed countries, and is responsible for one third or more of all deaths in individuals greater than 35 years [11,12] of age . World Health Organisation has projected that burden due to CAD is going to increase globally from 47 million disability adjusted life years (DALYs) in 1990 to about 82 million DALYs in 2020. Many studies have demonstrated that young CAD contributes to [13] 2% to 6% of all acute coronary events . In the early 1980s, the Framingham study (FHS) reported a 10 year CAD incidence of 12.9 per 1000 in the age of 30 to 34 years and 5.2 per 1000 in the age group 35 to 44 [14] years, in men and women respectively . Studies have shown an increased prevalence of CAD in the subjects with family history of premature [15] CAD, than in general population (35% vs 14%) . The original as well as offspring cohort data of Framingham study, by National heart lung and blood institute (NHLBI’s), from 1880 to 2003 revealed an annual incidence of cardiovascular disease of 3 per 1000 men [16] between 35 to 44 years of age . Centre of disease control prevalence data for the year 2010 revealed that prevalence of CAD in the age group of 18 to 44 years, 45 to 64 years and more than 65 years was 1.2%, [17] 7.1% and 19.8% respectively . Epidemiological data of United Kingdom published in the year 2000, reported a prevalence of 0.5% and 0.18% in men and women [1] between 35 to 44 years respectively . The prevalence of occult CAD in 112 asymptomatic young individuals, less than 40 years of age, was found to be 11% (9 had
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Terminology
RISK FACTORS PROFILE Conventional risk factors (Table 2)
Prevalence of conventional risk factors like diabetes, hypertension, smoking, dyslipidemia and obesity accounts for about 85% to 90% of premature CAD [22] patients . Often young CAD patients have multiple [23] coexisting risk factors contributing to the disease . The most common risk factor associated with young CAD seems to be smoking. The prevalence of smoking in younger individuals less than 45 years of age, with CAD, was reported to be 60% to 90% as compared to 24% [13,24] to 56% in subjects greater than 45 years . Smoking in presence of additional risk factors like diabetes, hypertension and obesity predispose a young individual [25] to increased risk of future acute coronary events . The prevalence of diabetes and hypertension seems to higher in young patients with CAD than without CAD. The prevalence of hypertension is 25% in young
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circumference . Family history of premature CAD is an important risk factor for young CAD. It stresses the role of genes in the aetiology of young CAD. Studies have shown that person with a positive family history of premature CAD tend to have severe coronary atherosclerosis and is a [32] very strong predictor of future acute coronary event . The atherosclerosis in coronary vessels, as revealed by increased plaque content is seen in individuals with a positive family history of premature CAD and increases [32] the incidence of severe obstructive CAD . One study revealed around 64% of young CAD patients had a [13] positive family history . The prevalence of conventional risk factors like hypertension (67%), dyslipidemia (67%), obesity (53%), smoking (42%), and diabetes (33%) is higher [33] in women with a family history of CAD .
Table 2 List of conventional and newer risk factors in young coronary artery disease discussed in the review Conventional risk factors Age Sex Hypertension Diabetes mellitus Dyslipidaemia Obesity Smoking Family history of premature CAD
Newer risk factors Polymorphisms in CETP gene Hepatic lipase gene Lipoprotein lipase gene C-reactive protein gene Apo A1 gene Apo B gene Apo E gene HIF1A gene Factor 5 leiden MTHFR gene Methionine synthase gene Cocaine use Lipoprotein-a, Fibrinogen and D-dimer Decreased serum Wnt Increased gamma glutamyl transferase Raised vitamin D2 and D3 Decreased osteocalcin Hypothyroidism Systemic lupus erythematosis Rheumatoid arthritis HIV patients on HAART Homocysteinemia Kawasaki disease in childhood, Patent foramen ovale Spontaneous coronary artery dissection
Other risk factors
There are numerous risk factors found to be associated with CAD in younger people. Some of the newer risk factors are discussed in the review. Polymorphisms in cholesterol ester transfer protein (CETP) gene, hepatic lipase gene, lipoprotein lipase gene, C-reactive protein gene, apo A1 gene, apo E gene, apo B, hypoxia inducible factor 1 alpha gene, factor 5 leiden, Methylene tetrahydrofolate reductase (MTHFR) gene and methion ine synthase gene have been associated with premature [34-38] CAD . [39] Kuivenhoven et al found a significant association between variation at the CETP locus and angiographic progression of coronary atherosclerosis in men with CHD. The ApoE4 allele has been associated with CAD in several populations. ApoE2/E2 homozygous individuals are at risk for type III hyperlipoproteinemia, which is [40,41] associated with an increased risk for atherosclerosis . Homozygosity for the MTHFR C677T mutation has been associated with elevated levels of homocysteine, and homocysteine levels have been associated with [42,43] CAD risk . Hepatic lipase (HL) is both a phospholipase and a triglyceride lipase and plays an important role in HDL metabolism and in the conversion of VLDL to LDL. Single nucleotide polymorphisms in the HL gene have been shown to associate with plasma lipid concen [44] trations and increased CHD risk . Hypercholesterolemia is the most common and treatable cause of heart disease. Familial Hypercholestero lemia (FH) results from mutations in the LDL receptor, ApoB, PCSK9, and ApoE genes. FH is characterized by isolated elevation of plasma low-density lipoprotein cholesterol and is associated with high risk of premature [45] cardiovascular disease . The prevalence of premature arcus senilis (16.1%), premature greying (34.9%) and premature balding (22.3%) have been found to be significantly increased in young CAD patients when compared to non CAD
CETP: Cholesterol ester transfer protein; HAART: Highly active anti retroviral therapy; MTHFR: Methylene tetrahydrofolate reductase; HIF1A: Hypoxia inducible factor 1 alpha.
CAD as compared to 13% without CAD. Similarly, the incidence of diabetes and pre diabetes is 14.3% and 7.6% in young CAD as compared to only 5.4% and [26] 4.3% in patients without CAD respectively . However, prevalence of these risk factors is much higher in older [27-29] individuals with CAD as compared to young CAD . Various studies have demonstrated a recent increase in the prevalence of hypertension [8.86% (2001-2002) to 27.7% (2009-2010)] and dysglycemia [7.6% [30] (2001-2002) to 36.15% (2009-2010)] in young CAD . Although, dyslipidemia is an important risk factor for young CAD, there seems to be a little difference in prevalence of lipid abnormalities in younger and older patients. One study demonstrated a significantly increased level of LDL and total cholesterol in persons of CAD more than 55 years of age when compared with [27] less than 55 years of age . Conversely in an another study there is high prevalence of lipid abnormalities [28] in young CAD when compared to older CAD group . These differences in lipid parameters may due effect of dietary, genetic and environmental factors on lipid metabolism. Obesity is a well established risk factor for CAD. There is little difference in the prevalence of obesity in [28] young CAD when compared with older CAD patients . Sagittal abdominal diameter to skin fold ratio seems to be a good indicator in predicting premature CAD, even better than body mass index (BMI) and waist
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subjects of same age . Thus young CAD patients are associated with premature ageing as depicted by these markers. The arcus senilis is also a marker of familial hypercholesterolemia which in turn is a risk factor for premature CAD. Cocaine use is also considered as a risk factor for CAD, it is associated with a number of cardiovascular diseases, including myocardial infarction, heart failure, cardiomyopathies, arrhythmias, aortic dissection, and [47] endocarditis . Young CAD patient shows an increased serum levels of lipoprotein-a, fibrinogen and D-dimer as compared [8] to age matched controls . Decreased serum Wnt, increased gamma glutamyl transferase, raised vitamin D2 and D3 and decreased levels of osteocalcin are [48-50] found to be associated with premature CAD . This association of CAD in young with high levels of vitamin D is in contradiction to the studies done in general population where deficiency of vitamin D is associated [51-53] with adverse cardiovascular outcomes . Diseases such as hypothyroidism, systemic lupus erythematosis, rheumatoid arthritis, HIV patients on highly active anti retroviral therapy (HAART) (especially with protease inhibitors), homocysteinaemia, kawasaki disease in childhood, patent foramen ovale (causing paradoxical embolism) and various other conditions are [54,55] found to associated with accelerated atherosclerosis . The mean age of presentation of spontaneous coronary artery dissection is 35-40 years, and is more common in females. The patients are divided into three groups: A peripartum, atherosclerotic and idiopathic [56] group . Dissection occurs in tunica intima of coronary arteries, the blood penetrates and results in intramural hematoma in tunica media, resulting in restriction in the size of lumen, reduction of blood flow and myocardial [57] infarction .
CAD
PROGNOSIS Obesity and current smoking are the two important conventional risk factors associated with adverse outcomes in the form of increased mortality and future [3] acute coronary events . Mortality of CAD in people of China, less than 40 years of age, was 13.81/100000 [61] in 2006 which increased to 19.07/100000 in 2009 . There is a widespread decrease in mortality due to CAD in older age group in the recent years but it not seen in [62] CAD in younger age group . The possible explanation that is proposed is increase in prevalence of risk factors such as diabetes, obesity and hypertension in younger [62] age groups . Mortality after an acute coronary event is two times higher in women than in men under 50 years [63,64] of age . The cause of increased incidence of adverse event in women with premature CAD is still unknown. In patient with acute coronary event both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are associated with excellent immediate survival (mortality of 0.8% vs 1.4% for PCI and CABG respectively at 30 d) as well as [65] long term survival outcomes at end of 5 years . But PCI seems to associated with lower rate of repeated acute coronary events and revascularisation procedures when compared to CABG at the end of 5 years (repeat myocardial infarction 89.9% vs 96.6% for PCI vs [66] CABG) . Mortality outcomes at 30 d and 3 years after an ST segment elevation myocardial infarction in 3601 patients with and without family history of premature CAD were compared in Harmonizing outcomes with revascularization and stents in acute myocardial infarction (HORIZONS-AMI) trial, which did not show any significant association of family history of premature [67] CAD with mortality outcomes . In patients with young CAD high C-reactive protein have been associated recurrence of future acute coronary event and raised fibrinogen levels seems to be associated with increased [6] mortality . Persons with positive family history of premature CAD and coronary artery calcium scores th greater than 80 percentiles benefit from treatment with statins for primary prevention of acute coronary [68] events . Young CAD patients have higher rates of normal coronary vessels on angiography, mild luminal irregu larities and increased prevalence of single vessel disease [24] than older CAD patients . In recent study from Nepal of young CAD less than 45 years angiography revealed 7.6% had normal or non critical disease, 6.1% had triple vessel disease, 36.9% had double vessel disease [69] and 53.8% had single vessel disease . Single vessel disease involving left anterior des cending artery is much more common in young women [70,71] when compared with young men with CAD . The prevalence of normal coronary arteries in patients with young CAD is about 8% to 22% as reported in [72-74] various studies compared to 3% to 4% in general
PATHOPHYSIOLOGY OF CAD IN YOUNG Conventional CAD accounts for about 80% of CAD in young adults. About 4% of heart attacks in young adults are due to congenital abnormalities of the coronary artery anatomy, about 5% due to blood clots that originate elsewhere and are carried to otherwise normal coronary arteries, and block the artery, in another 5%, various disorders of the blood clotting system increase the risk of clot formation. The remaining 6% of CAD in young adults is due to spasm or inflammation of the coronary arteries, radiation therapy for chest tumors, chest trauma, and abuse of cocaine, amphetamines, and other drugs. Coronary segments, with non-signifi cant stenosis and non calcified plaque, shows positive remodeling that might be the cause of CAD in young individuals with normal coronary artery. Positive remodeling is related to plaque instability, suggesting it is more prone to rupture and erosion with subsequent coronary events. Lipid core plaques, in contrast to the severely calcified plaques, showed positive vascular remodeling, thus early plaques are more prone for
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CAD population . The cause of this high prevalence of normal angiography in young CAD patients is still unclear. The probable reason could be the natural extra luminal progression of disease in the initial stages, as the vessel wall compensates to maintain unrestricted luminal [76] blood flow . An occlusive thrombus produced by the rupture of an angiographically “invisible” vulnerable plaque totally lysed after few hours or a long-lasting vasospasm leading to complete occlusion of a normal coronary artery or a combination of these two are the most likely mechanism of CAD in patient with normal [77] coronaries .
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CONCLUSION The overall prevalence of CAD including the subset of young CAD is on decreasing trend but mortality of CAD doesn’t seems to be decreasing when comparing to older CAD patients. In addition to conventional risk factors numerous other risk factors and genes play an important role in the causation of the disease. The prognosis of CAD in younger people is better than older people. Current smoking and obesity have major impact in long term mortality and morbidity. Young CAD patients with an acute coronary event undergoing PCI and CABG have an excellent immediate and long term survival rates.
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REFERENCES 1 2
3
4
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Egred M, Viswanathan G, Davis GK. Myocardial infarction in young adults. Postgrad Med J 2005; 81: 741-745 [PMID: 16344295 DOI: 10.1136/pgmj.2004.027532] Ericsson CG, Hamsten A, Nilsson J, Grip L, Svane B, de Faire U. Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet 1996; 347: 849-853 [PMID: 8622389 DOI: 10.1016/ S0140-6736(96)91343-4] Konishi H, Miyauchi K, Kasai T, Tsuboi S, Ogita M, Naito R, Katoh Y, Okai I, Tamura H, Okazaki S, Daida H. Long-term prognosis and clinical characteristics of young adults (≤40 years old) who underwent percutaneous coronary intervention. J Cardiol 2014; 64: 171-174 [PMID: 24495504 DOI: 10.1016/j.jjcc.2013.12.005] Gupta R, Misra A, Vikram NK, Kondal D, Gupta SS, Agrawal A, Pandey RM. Younger age of escalation of cardiovascular risk factors in Asian Indian subjects. BMC Cardiovasc Disord 2009; 9: 28 [PMID: 19575817 DOI: 10.1186/1471-2261-9-28] Christus T, Shukkur AM, Rashdan I, Koshy T, Alanbaei M, Zubaid M, Hayat N, Alsayegh A. Coronary Artery Disease in Patients Aged 35 or less - A Different Beast? Heart Views 2011; 12: 7-11 [PMID: 21731802 DOI: 10.4103/1995-705X.81550] van Loon JE, de Maat MP, Deckers JW, van Domburg RT, Leebeek FW. Prognostic markers in young patients with premature coronary heart disease. Atherosclerosis 2012; 224: 213-217 [PMID: 22818563 DOI: 10.1016/j.atherosclerosis.2012.06.067] Genest JJ, McNamara JR, Salem DN, Schaefer EJ. Prevalence of risk factors in men with premature coronary artery disease. Am J Cardiol 1991; 67: 1185-1189 [PMID: 2035438 DOI: 10.1016/00029149(91)90924-A] Pineda J, Marín F, Marco P, Roldán V, Valencia J, Ruiz-Nodar JM, Sogorb F, Lip GY. Premature coronary artery disease in young (age & lt; 45) subjects: interactions of lipid profile, thrombophilic and haemostatic markers. Int J Cardiol 2009; 136: 222-225 [PMID: 18625524 DOI: 10.1016/j.ijcard.2008.04.020]
WJC|www.wjgnet.com
16
17 18
19
20 21
22
732
Norum RA, Lakier JB, Goldstein S, Angel A, Goldberg RB, Block WD, Noffze DK, Dolphin PJ, Edelglass J, Bogorad DD, Alaupovic P. Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease. N Engl J Med 1982; 306: 1513-1519 [PMID: 7078608 DOI: 10.1056/NEJM198206243062503] Iribarren C, Go AS, Husson G, Sidney S, Fair JM, Quertermous T, Hlatky MA, Fortmann SP. Metabolic syndrome and earlyonset coronary artery disease: is the whole greater than its parts? J Am Coll Cardiol 2006; 48: 1800-1807 [PMID: 17084253 DOI: 10.1016/j.jacc.2006.03.070] Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 2010; 121: 948-954 [PMID: 20177011 DOI: 10.1161/ CIRCULATIONAHA.109.192666] Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: epidemiological update. Eur Heart J 2014; 35: 2929 [PMID: 25381246 DOI: 10.1093/eurheartj/ehu299] Cole JH, Miller JI, Sperling LS, Weintraub WS. Long-term followup of coronary artery disease presenting in young adults. J Am Coll Cardiol 2003; 41: 521-528 [PMID: 12598059 DOI: 10.1016/ S0735-1097(02)02862-0] Kannel WB, Abbott RD. Incidence and prognosis of unrecognized myocardial infarction. An update on the Framingham study. N Engl J Med 1984; 311: 1144-1147 [PMID: 6482932 DOI: 10.1056/ NEJM198411013111802] Kang MK, Chang HJ, Kim YJ, Park AR, Park S, Jang Y, Chung N. Prevalence and determinants of coronary artery disease in first-degree relatives of premature coronary artery disease. Coron Artery Dis 2012; 23: 167-173 [PMID: 22421547 DOI: 10.1097/ MCA.0b013e3283515538] Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Roger VL, Thom T, WasserthielSmoller S, Wong ND, Wylie-Rosett J. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 2010; 121: e46-e215 [PMID: 20019324 DOI: 10.1161/CIRCULATIONAHA.109.192667] Centers for Disease Control and Prevention (CDC). Prevalence of coronary heart disease--United States, 2006-2010. MMWR Morb Mortal Wkly Rep 2011; 60: 1377-1381 [PMID: 21993341] Ha EJ, Kim Y, Cheung JY, Shim SS. Coronary artery disease in asymptomatic young adults: its prevalence according to coronary artery disease risk stratification and the CT characteristics. Korean J Radiol 2010; 11: 425-432 [PMID: 20592926 DOI: 10.3348/ kjr.2010.11.4.425] Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937-952 [PMID: 15364185 DOI: 10.1016/ S0140-6736(04)17018-9] Sharma M, Ganguly NK. Premature coronary artery disease in Indians and its associated risk factors. Vasc Health Risk Manag 2005; 1: 217-225 [PMID: 17319107] Kam R, Cutter J, Chew SK, Tan A, Emmanuel S, Mak KH, Chan CN, Koh TH, Lim YL. Gender differences in outcome after an acute myocardial infarction in Singapore. Singapore Med J 2002; 43: 243-248 [PMID: 12188076] Khot UN, Khot MB, Bajzer CT, Sapp SK, Ohman EM, Brener SJ, Ellis SG, Lincoff AM, Topol EJ. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 2003; 290:
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29
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33
34
35
36
898-904 [PMID: 12928466 DOI: 10.1001/jama.290.7.898] Celik T, Iyisoy A. Premature coronary artery disease in young patients: an uncommon but growing entity. Int J Cardiol 2010; 144: 131-132 [PMID: 19174320 DOI: 10.1016/j.ijcard.2008.12.150] Zimmerman FH, Cameron A, Fisher LD, Ng G. Myocardial infarction in young adults: angiographic characterization, risk factors and prognosis (Coronary Artery Surgery Study Registry). J Am Coll Cardiol 1995; 26: 654-661 [PMID: 7642855 DOI: 10.1016 /0735-1097(95)00254-2] Aggarwal A, Aggarwal S, Sarkar PG, Sharma V. Predisposing factors to premature coronary artery disease in young (age ≤ 45 years) smokers: a single center retrospective case control study from India. J Cardiovasc Thorac Res 2014; 6: 15-19 [PMID: 24753826] Aggarwal A, Aggarwal S, Goel A, Sharma V, Dwivedi S. A retrospective case-control study of modifiable risk factors and cutaneous markers in Indian patients with young coronary artery disease. JRSM Cardiovasc Dis 2012; 1: pii: cvd.2012.012010 [PMID: 24175065 DOI: 10.1258/cvd.2012.012010] Hatmi ZN, Mahdavi-Mazdeh M, Hashemi-Nazari SS, Hajighasemi E, Nozari B, Mahdavi A. Pattern of coronary artery disease risk factors in population younger than 55 years and above 55 years: a population study of 31999 healthy individuals. Acta Med Iran 2011; 49: 368-374 [PMID: 21874640] Sinha N, Kumar S, Rai H, Singh N, Kapoor A, Tewari S, Saran RK, Narain VS, Bharadwaj RP, Bansal RK, Saxena PC, Sinha PR, Gupta PR, Mishra M, Jain P, Pandey CM, Singh U, Agarwal SS. Patterns and determinants of dyslipidaemia in ‘Young’ versus ‘Not so Young’ patients of coronary artery disease: a multicentric, randomised observational study in northern India. Indian Heart J 2012; 64: 229-235 [PMID: 22664802 DOI: 10.1016/S0019-4832(12)60078-9] Reibis R, Treszl A, Wegscheider K, Bestehorn K, Karmann B, Völler H. Disparity in risk factor pattern in premature versus lateonset coronary artery disease: a survey of 15,381 patients. Vasc Health Risk Manag 2012; 8: 473-481 [PMID: 22930639 DOI: 10.2147/VHRM.S33305] Aggarwal A, Aggarwal S, Sharma V. Cardiovascular Risk Factors in Young Patients of Coronary Artery Disease: Differences over a Decade. J Cardiovasc Thorac Res 2014; 6: 169-173 [PMID: 25320664 DOI: 10.15171/jcvtr.2014.006] Vasheghani-Farahani A, Majidzadeh-A K, Masoudkabir F, Karbalai S, Koleini M, Aiatollahzade-Esfahani F, Pashang M, Hakki E. Sagittal abdominal diameter to triceps skinfold thickness ratio: a novel anthropometric index to predict premature coronary atherosclerosis. Atherosclerosis 2013; 227: 329-333 [PMID: 23466099 DOI: 10.1016/j.atherosclerosis.2013.01.033] Otaki Y, Gransar H, Berman DS, Cheng VY, Dey D, Lin FY, Achenbach S, Al-Mallah M, Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Chinnaiyan K, Chow BJ, Delago A, Hadamitzky M, Hausleiter J, Kaufmann P, Maffei E, Raff G, Shaw LJ, Villines TC, Dunning A, Min JK. Impact of family history of coronary artery disease in young individuals (from the CONFIRM registry). Am J Cardiol 2013; 111: 1081-1086 [PMID: 23411105 DOI: 10.1016/ j.amjcard.2012.12.042] Choi J, Daskalopoulou SS, Thanassoulis G, Karp I, Pelletier R, Behlouli H, Pilote L. Sex- and gender-related risk factor burden in patients with premature acute coronary syndrome. Can J Cardiol 2014; 30: 109-117 [PMID: 24238757 DOI: 10.1016/ j.cjca.2013.07.674] Anderson JL, Horne BD, Camp NJ, Muhlestein JB, Hopkins PN, Cannon-Albright LA, Mower CP, Park JJ, Clarke JL, Nicholas ZP, McKinney JT, Carlquist JF. Joint effects of common genetic variants from multiple genes and pathways on the risk of premature coronary artery disease. Am Heart J 2010; 160: 250-256.e3 [PMID: 20691829] Abd El-Aziz TA, Mohamed RH. Human C-reactive protein gene polymorphism and metabolic syndrome are associated with premature coronary artery disease. Gene 2013; 532: 216-221 [PMID: 24055729 DOI: 10.1016/j.gene.2013.09.042] Kay A, März W, Hoffmann MM, Zhang Q, Masana Ll, Cavanna J, Baroni MG, Shine B, Galton DJ. Coronary artery disease and
WJC|www.wjgnet.com
37
38
39
40
41 42
43
44 45
46
47 48
49
50
733
dyslipidemia within Europe: genetic variants in lipid transport gene loci in German subjects with premature coronary artery disease. Atheroscler Suppl 2002; 3: 27-33 [PMID: 12044583 DOI: 10.1016/ S1567-5688(01)00003-4] López-Reyes A, Rodríguez-Pérez JM, Fernández-Torres J, Martínez-Rodríguez N, Pérez-Hernández N, Fuentes-Gómez AJ, Aguilar-González CA, Alvarez-León E, Posadas-Romero C, Villarreal-Molina T, Pineda C, Vargas-Alarcón G. The HIF1A rs2057482 polymorphism is associated with risk of developing premature coronary artery disease and with some metabolic and cardiovascular risk factors. The Genetics of Atherosclerotic Disease (GEA) Mexican Study. Exp Mol Pathol 2014; 96: 405-410 [PMID: 24769354 DOI: 10.1016/j.yexmp.2014.04.010] Kanth VV, Golla JP, Sastry BK, Naik S, Kabra N, Sujatha M. Genetic interactions between MTHFR (C677T), methionine synthase (A2756G, C2758G) variants with vitamin B12 and folic acid determine susceptibility to premature coronary artery disease in Indian population. J Cardiovasc Dis Res 2011; 2: 156-163 [PMID: 22022143 DOI: 10.4103/0975-3583.85262] Kuivenhoven JA, Jukema JW, Zwinderman AH, de Knijff P, McPherson R, Bruschke AV, Lie KI, Kastelein JJ. The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group. N Engl J Med 1998; 338: 86-93 [PMID: 9420339 DOI: 10.1056/NEJM199801083380203] Nieminen MS, Mattila KJ, Aalto-Setälä K, Kuusi T, Kontula K, Kauppinen-Mäkelin R, Ehnholm C, Jauhiainen M, Valle M, Taskinen MR. Lipoproteins and their genetic variation in subjects with and without angiographically verified coronary artery disease. Arterioscler Thromb 1992; 12: 58-69 [PMID: 1346250 DOI: 10.1161/01. ATV.12.1.58] Eto M, Watanabe K, Makino I. Increased frequencies of apoli poprotein epsilon 2 and epsilon 4 alleles in patients with ischemic heart disease. Clin Genet 1989; 36: 183-188 [PMID: 2791332] Brattström L, Wilcken DE, Ohrvik J, Brudin L. Common methy lenetetrahydrofolate reductase gene mutation leads to hyperhomo cysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 1998; 98: 2520-2526 [PMID: 9843457 DOI: 10.1161/01. CIR.98.23.2520] Danesh J, Lewington S. Plasma homocysteine and coronary heart disease: systematic review of published epidemiological studies. J Cardiovasc Risk 1998; 5: 229-232 [PMID: 9919470 DOI: 10.1097/ 00043798-199808000-00004] Chatterjee C, Sparks DL. Hepatic lipase, high density lipoproteins, and hypertriglyceridemia. Am J Pathol 2011; 178: 1429-1433 [PMID: 21406176 DOI: 10.1016/j.ajpath.2010.12.050] Setia N, Verma IC, Khan B, Arora A. Premature coronary artery disease and familial hypercholesterolemia: need for early diagnosis and cascade screening in the Indian population. Cardiol Res Pract 2012; 2012: 658526 [PMID: 22111029 DOI: 10.1155/2012/658526] Erdoğan T, Kocaman SA, Çetin M, Durakoğlugil ME, Uğurlu Y, Şahin İ, Çanga A. Premature hair whitening is an independent predictor of carotid intima-media thickness in young and middleaged men. Intern Med 2013; 52: 29-36 [PMID: 23291671 DOI: 10.2169/internalmedicine.52.7842] Rezkalla SH, Kloner RA. Cocaine-induced acute myocardial infarction. Clin Med Res 2007; 5: 172-176 [PMID: 18056026 DOI: 10.3121/cmr.2007.759] Shabbir S, Khan DA, Khan FA, Elahi MM, Matata BM. Serum gamma glutamyl transferase: a novel biomarker for screening of premature coronary artery disease. Cardiovasc Revasc Med 2011; 12: 367-374 [PMID: 21454140 DOI: 10.1016/j.carrev.2011.02.001] Goliasch G, Blessberger H, Azar D, Heinze G, Wojta J, Bieglmayer C, Wagner O, Schillinger M, Huber K, Maurer G, Haas M, Wiesbauer F. Markers of bone metabolism in premature myocardial infarction (≤ 40 years of age). Bone 2011; 48: 622-626 [PMID: 21078422 DOI: 10.1016/j.bone.2010.11.005] Goliasch G, Wiesbauer F, Kastl SP, Katsaros KM, Blessberger H, Maurer G, Schillinger M, Huber K, Wojta J, Speidl WS. Premature myocardial infarction is associated with low serum levels of Wnt-1.
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Atherosclerosis 2012; 222: 251-256 [PMID: 22391424 DOI: 10.1016/j.atherosclerosis.2012.02.017] Sood A, Arora R. Vitamin D deficiency and its correlations with increased cardiovascular incidences. Am J Ther 2010; 17: e105-e109 [PMID: 19451805] Michos ED, Melamed ML. Vitamin D and cardiovascular disease risk. Curr Opin Clin Nutr Metab Care 2008; 11: 7-12 [PMID: 18090651 DOI: 10.1097/MCO.0b013e3282f2f4dd] Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Inde pendent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 2008; 168: 1340-1349 [PMID: 18574092 DOI: 10.1001/archinte.168.12.1340] Othman KMS, Assaf NY. Early detection of premature subclinical coronary atherosclerosis in systemic lupus erythematosus patients. The Egyptian Heart Journal 2013; 65: 281-288 [DOI: 10.1016/ j.ehj.2012.12.003] de Saint Martin L, Vandhuick O, Guillo P, Bellein V, Bressollette L, Roudaut N, Amaral A, Pasquier E. Premature atherosclerosis in HIV positive patients and cumulated time of exposure to antiretroviral therapy (SHIVA study). Atherosclerosis 2006; 185: 361-367 [PMID: 16137695 DOI: 10.1016/j.atherosclerosis.2005.06.049] DeMaio SJ, Kinsella SH, Silverman ME. Clinical course and longterm prognosis of spontaneous coronary artery dissection. Am J Cardiol 1989; 64: 471-474 [PMID: 2773790 DOI: 10.1016/0002-91 49(89)90423-2] Dhawan R, Singh G, Fesniak H. Spontaneous coronary artery dissection: the clinical spectrum. Angiology 1979; 53: 89-93 [PMID: 11863314 DOI: 10.1177/000331970205300112] Klein LW. Acute coronary syndromes in young patients with angiographically normal coronary arteries. Am Heart J 2006; 152: 607-610 [PMID: 16996822 DOI: 10.1016/j.ahj.2006.03.020] Tanaka M, Tomiyasu K, Fukui M, Akabame S, KobayashiTakenaka Y, Nakano K, Kadono M, Hasegawa G, Oda Y, Nakamura N. Evaluation of characteristics and degree of remodeling in coronary atherosclerotic lesions by 64-detector multislice computed tomography (MSCT). Atherosclerosis 2009; 203: 436-441 [PMID: 18775536 DOI: 10.1016/j.atherosclerosis.2008.07.013] Kullo IJ, Edwards WD, Schwartz RS. Vulnerable plaque: pathobiology and clinical implications. Ann Intern Med 1998; 129: 1050-1060 [PMID: 9867761 DOI: 10.7326/0003-4819-129-12-199 812150-00010] Yang WX, Yang Z, Wu YJ, Qiao SB, Yang YJ, Chen JL. Factors associated with coronary artery disease in young population (age ≤ 40): analysis with 217 cases. Chin Med Sci J 2014; 29: 38-42 [PMID: 24698677 DOI: 10.1016/S1001-9294(14)60022-5] Nichols M, Townsend N, Scarborough P, Rayner M. Trends in agespecific coronary heart disease mortality in the European Union over three decades: 1980-2009. Eur Heart J 2013; 34: 3017-3027 [PMID: 23801825] Sharma K, Gulati M. Coronary artery disease in women: a 2013 update. Glob Heart 2013; 8: 105-112 [PMID: 25690374 DOI: 10.1016/j.gheart.2013.02.001] Vaccarino V, Badimon L, Corti R, de Wit C, Dorobantu M, Manfrini O, Koller A, Pries A, Cenko E, Bugiardini R. Presentation, management, and outcomes of ischaemic heart disease in women. Nat Rev Cardiol 2013; 10: 508-518 [PMID: 23817188 DOI: 10.1038/nrcardio.2013.93] Fournier JA, Sánchez A, Quero J, Fernández-Cortacero JA, González-Barrero A. Myocardial infarction in men aged 40 years or less: a prospective clinical-angiographic study. Clin Cardiol 1996;
66
67
68
69
70
71
72
73
74 75
76 77
19: 631-636 [PMID: 8864336 DOI: 10.1002/clc.4960190809] Biancari F, Gudbjartsson T, Heikkinen J, Anttila V, Mäkikallio T, Jeppsson A, Thimour-Bergström L, Mignosa C, Rubino AS, Kuttila K, Gunn J, Wistbacka JO, Teittinen K, Korpilahti K, Onorati F, Faggian G, Vinco G, Vassanelli C, Ribichini F, Juvonen T, Axelsson TA, Sigurdsson AF, Karjalainen PP, Mennander A, Kajander O, Eskola M, Ilveskoski E, D’Oria V, De Feo M, Kiviniemi T, Airaksinen KE. Comparison of 30-day and 5-year outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in patients aged≤50 years (the Coronary aRtery diseAse in younG adultS Study). Am J Cardiol 2014; 114: 198-205 [PMID: 24878127 DOI: 10.1016/j.amjcard.2014.04.025] Ertelt K, Généreux P, Mintz GS, Brener SJ, Kirtane AJ, McAndrew TC, Francese DP, Ben-Yehuda O, Mehran R, Stone GW. Clinical profile and impact of family history of premature coronary artery disease on clinical outcomes of patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: analysis from the HORIZONS-AMI Trial. Cardiovasc Revasc Med 2014; 15: 375-380 [PMID: 25288517 DOI: 10.1016/ j.carrev.2014.09.002] Mulders TA, Sivapalaratnam S, Stroes ES, Kastelein JJ, Guerci AD, Pinto-Sietsma SJ. Asymptomatic individuals with a positive family history for premature coronary artery disease and elevated coronary calcium scores benefit from statin treatment: a post hoc analysis from the St. Francis Heart Study. JACC Cardiovasc Imaging 2012; 5: 252-260 [PMID: 22421169 DOI: 10.1016/ j.jcmg.2011.11.014] Tamrakar R, Bhatt YD, Kansakar S, Bhattarai M, Shaha KB, Tuladhar E. Acute Myocardial Infarction in Young Adults: Study of Risk factors, Angiographic Features and Clinical Outcome. Nepalese Heart Journal 2014; 10: 12-16 [DOI: 10.3126/njh. v10i1.9740] Li Z, Li ZZ, Gao YL, Tao Y, Wang S, Wang Q, Ma CS, DU X. Clinical and coronary angiographic features of young women with acute myocardial infarction. Zhonghua Xinxue Guanbing Zazhi 2012; 40: 225-230 [PMID: 22801268] Liu W, Mukku VK, Liu YY, Shi DM, Zhao YX, Zhou YJ. Longterm follow up of percutaneous coronary intervention of coronary artery disease in women ≤45 years of age. Am J Cardiol 2013; 112: 918-922 [PMID: 23791012 DOI: 10.1016/j.amjcard.2013.05.027] Kaul U, Dogra B, Manchanda SC, Wasir HS, Rajani M, Bhatia ML. Myocardial infarction in young Indian patients: risk factors and coronary arteriographic profile. Am Heart J 1986; 112: 71-75 [PMID: 3728290 DOI: 10.1016/0002-8703(86)90680-0] Gohlke H, Gohlke-Bärwolf C, Stürzenhofecker P, Görnandt L, Thilo A, Haakshorst W, Roskamm H. Myocardial Infarction at young age - correlation of angio-graphic findings with risk factors and history in 619 patients. Circulation 1980; (Suppl III) 62: 39 (abstr) Lim YT, Ling LH, Tambyah PA, Choo MH. Myocardial infarction in patients aged 40 years and below: an angiographic review. Singapore Med J 1996; 37: 352-355 [PMID: 8993130] Agewall S, Eurenius L, Hofman-Bang C, Malmqvist K, Frick M, Jernberg T, Tornvall P. Myocardial infarction with angiographically normal coronary arteries. Atherosclerosis 2011; 219: 10-14 [PMID: 21601856 DOI: 10.1016/j.atherosclerosis.2011.04.036] Chandrasekaran B, Kurbaan AS. Myocardial infarction with angiographically normal coronary arteries. J R Soc Med 2002; 95: 398-400 [PMID: 12151489 DOI: 10.1258/jrsm.95.8.398] Alpert JS. Myocardial infarction with angiographically normal coronary arteries. Arch Intern Med 1994; 154: 265-269 [PMID: 8297192 DOI: 10.1001/archinte.154.3.265] P- Reviewer: Pocar M, Sabate M, Tsai WC S- Editor: Ji FF L- Editor: A E- Editor: Wu HL
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